P1111: COMPARATIVE EFFICACY AND SAFETY OF TISAGENLECLEUCEL AND AXICABTAGENE CILOLEUCEL IN RELAPSED/REFRACTORY FOLLICULAR LYMPHOMA
Authors: M. Dickinson, J. Martinez-Lopez, E. Jousseaume, C. Anjos, H. Yang, X. Chai, T. Wang, R. Ramos, C. Lobetti-Bodoni, S. Schuster, N. Fowler
Journal: HemaSphere (2022)

Background: The chimeric antigen receptor T-cell (CAR-T) therapies, tisagenlecleucel (tisa-cel) and axicabtagene ciloleucel (axi-cel) have demonstrated clinical benefits in treating relapsed/refractory follicular lymphoma (r/r FL). Aims: To compare the efficacy and safety outcomes of tisa-cel and axi-cel in r/r FL using matching-adjusted indirect comparison (MAIC). Methods: Individual patient-level data (IPD) in ELARA (tisa-cel; NCT03568461; 03/2021 data-cut; N=97 [infused set]; N=90 [efficacy-evaluable set]) were weighted to match the patient population in ZUMA-5 (axi-cel; NCT03105336; 03/2020 data-cut; N=124 [infused set]; N=84 [efficacy-evaluable set]). Because patients from ZUMA-5 did not use bridging chemotherapy, the primary analysis compared a patient subgroup not exposed to bridging chemotherapy in ELARA (N=53 [infused set]; N=50 [efficacy-evaluable set]) with patients in ZUMA-5. Baseline characteristics available in both trials were adjusted in MAIC including age, sex, ECOG performance status, Ann Arbor stage, FLIPI, tumor burden per GELF criteria, number of prior therapy lines, refractory status to the most recent regimen, progression of disease within 24 months from first anti-CD20 monoclonal antibody-containing therapy, and prior autologous stem cell transplant. Efficacy outcomes, including overall response rate (ORR), complete response (CR) rate, and progression-free survival (PFS), were compared among the efficacy-evaluable set, defined as patients with ≥12 months of follow-up in both trials. Selected safety outcomes, including cytokine release syndrome (CRS), neurological events (NE), and tocilizumab and corticosteroid use for CRS, were compared between the infused populations. A sensitivity analysis was conducted to compare patients with and without bridging chemotherapy in ELARA with ZUMA-5. Results: After adjusting for differences in baseline characteristics, ORR, CR rate, and PFS were comparable between tisa-cel and axi-cel efficacy-evaluable patients (Figure 1A). In the primary analysis, the hazard ratio for PFS post-weighting was 0.90 (95% confidence interval: 0.39, 2.06; p=0.81) (Figure 1B). The adverse event rates for CRS and NE of any grade were 32.70% (p<0.01) and 47.70% (p<0.001) lower, respectively, in patients infused with tisa-cel compared to those infused with axi-cel. The proportion of patients who used tocilizumab and corticosteroids for CRS were 35.57% (p<0.001) and 12.69% (p<0.01) lower, respectively, in patients infused with tisa-cel (Figure 1C). Similar results were observed in the sensitivity analysis among patients with and without bridging chemotherapy in ELARA (Figure 1A-C). Image:Summary/Conclusion: The MAIC results indicated that tisa-cel and axi-cel were comparable in response rates and PFS, while tisa-cel was associated with better safety outcomes than axi-cel. These results confirm and reinforce the relevance of CAR-T therapies for r/r FL. Future analyses using IPD from both trials and real-world data are warranted.